Cardiac Safety Study in Patients With HER2 + Breast Cancer

NCT01904903 | Completed Phase 2 Results DMC

• 1 other identifier: ML 28685
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

HER2 positive breast cancer cells have more HER2 receptor (a protein on the surface of cells) than normal breast cells. Approximately 30% of patients with breast cancer have HER2 positive breast cancer. Before HER2 targeted therapies (i.e. treatments that directly block the receptor HER2) were developed, patients with HER2 positive breast cancer had a very aggressive form of disease. With the use of trastuzumab, an anticancer drug that directly targets the receptor HER2, and more recently, pertuzumab and ado-trastuzumab emtansine, patients are able to live longer and have better control of their cancer. Unfortunately the use of HER2 targeted therapies can increase the risk of heart problems and for this reason these treatments were only studied and approved for patients with normal heart function. In this study we plan to give HER2 targeted therapies to patients with HER2 positive breast cancer and mildly decreased heart function along with concomitant evaluation by a heart doctor (called cardiologist) and appropriate medications to strengthen the heart. We will do frequent monitoring of the heart function with a test called echocardiogram that will give us a detailed "picture" of the heart. We will also draw blood along with routine blood tests to try to understand why some patients develop heart problems and others do not. The study will take a maximum of 12 months and patients will be monitored for 6 additional months. We hypothesize that it is safe to administer HER2 targeted therapies to patients with breast cancer and mildly decreased heart function, i.e. LVEF between 40 and 50%, while on appropriate heart medications.

Conditions

HER2 Positive Breast Cancer; Left Ventricular Function Systolic Dysfunction

Keywords

Breast Cancer HER2 Positive; Cardiac Safety

Outcome Measures

Primary Outcomes (1)

• Percentage of Patients Who Complete Planned Oncologic Therapy Without the Development of a Cardiac Event or Asymptomatic Worsening of Cardiac Function.

  Cardiac events are defined as any of the following: * Presence of symptoms attributable to heart failure as confirmed by a cardiologist * Cardiac arrhythmia requiring pharmacological or electrical treatment * Myocardial infarction * Sudden cardiac death or death due to myocardial infarct, arrhythmia or heart failure Asymptomatic worsening of cardiac function defined as: \- Asymptomatic decline in LVEF \> 10% points from baseline and/or EF \< 35% corroborated by a confirmatory echocardiogram in 2-4 weeks Planned oncologic therapy is defined as: * In the adjuvant setting: completion of 1 year total of HER2 targeted therapy. If a patient already received part of the planned HER2 targeted therapy prior to enrollment in this trial, planned oncologic therapy will be achieved when a total of 1 year is completed. * In the metastatic setting: cessation of treating regimen due to progressive disease or non-cardiac toxicity or non-cardiac death.

  Up to 18 months.

Secondary Outcomes (5)

• Median Time to Development of an Event Defined as Cardiac Event or Asymptomatic Worsening of Left Ventricular Dysfunction, Among Patients Who Developed One Event.

  Up to 18 months.

• Absolute Changes in LVEF During HER2 Targeted Therapy Between Baseline and End of Treatment

  Up to 18 months.

• HER2 Therapy Holds Attributed to Proportion of Patients With Symptomatic or Asymptomatic Cardiotoxicity.

  Up to 12 months.

• Correlation of Global Longitudinal Myocardial Strain With Cardiac Events and Asymptomatic Worsening of Cardiac Function

  Up to 18 months.

• Correlation of Standard Cardiac Troponin I and Highly Sensitive Cardiac Troponin T With Cardiac Events and Asymptomatic Worsening of Cardiac Function

  Up to 18 months.

Study Arms (1)

HER2 therapies, cardiac medications

OTHER

Cardiac intervention - beta-blockers and ACE-inhibitors titrated to the maximum tolerated doses Oncology intervention - patients will receive one of the three following HER2 targeted therapies at the discretion of the treating oncologist: * Trastuzumab: loading dose of 8 mg/kg IV, followed by a maintenance dose of 6 mg/kg every 3 weeks, or a loading dose of 4 mg/kg followed by a maintenance dose of 2 mg/kg every week. * Pertuzumab: loading dose of 840 mg IV, followed by 420 mg IV every 3 weeks, administered concomitantly with trastuzumab. * Ado trastuzumab emtansine (TDM1): 3.6mg/kg IV every three weeks.

Drug: Trastuzumab; Drug: Pertuzumab; Drug: Ado Trastuzumab Emtansine

Interventions

Trastuzumab DRUG

HER2 therapy

Also known as: Herceptin

HER2 therapies, cardiac medications

Pertuzumab DRUG

HER2 therapy

Also known as: Perjeta

HER2 therapies, cardiac medications

Ado Trastuzumab Emtansine DRUG

HER2 therapy

Also known as: Kadcyla

HER2 therapies, cardiac medications

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male patient diagnosed with stage I-IV breast cancer
• HER2 positive breast cancer, defined by immunohistochemical staining for HER2 protein of 3+ intensity and/or amplification of the HER2 gene on fluorescence in situ hybridization (FISH) ≥ 2.0 on breast specimen or biopsy of a metastatic site
• LVEF \< 50% and ≥ 40% documented in echocardiogram done within the last 30 days
• HER2 therapy naïve or currently receiving non-lapatinib HER2 targeted therapy
• Patient receiving or planning to receive trastuzumab, trastuzumab with pertuzumab or ado-trastuzumab emtansine, for at least 3 months, alone or in combination with other systemic treatment or radiation
• Age ≥ 18 years
• Patient is willing and able to comply with protocol required assessments and procedures

You may not qualify if:

• Previous hospitalization due to documented heart failure in the last 12 months
• Current signs or symptoms of heart failure or ischemia
• History of arrhythmia requiring pharmacological or electrical treatment
• Concomitant use of anthracyclines or use of anthracyclines in the last 50 days
• Pregnant or lactating patients. Patients of childbearing potential must implement contraceptive measures during study treatment and for 7 months after last dose of treatment drug and must have negative urine or serum pregnancy test within 7 days prior to registration.
• History of significant neurologic or psychiatric disorders including psychotic disorders or dementia that would prohibit the understanding and giving of informed consent.

Sponsors & Collaborators

• Medstar Health Research Institute: lead
• Genentech, Inc.: collaborator

Study Sites (2)

Washington Cancer Institute at MedStar Washington Hospital Center

Washington D.C., District of Columbia, 20010, United States

Location

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, 20057, United States

Location

Related Publications (2)

• Lynce F, Barac A, Geng X, Dang C, Yu AF, Smith KL, Gallagher C, Pohlmann PR, Nunes R, Herbolsheimer P, Warren R, Srichai MB, Hofmeyer M, Cunningham A, Timothee P, Asch FM, Shajahan-Haq A, Tan MT, Isaacs C, Swain SM. Prospective evaluation of the cardiac safety of HER2-targeted therapies in patients with HER2-positive breast cancer and compromised heart function: the SAFE-HEaRt study. Breast Cancer Res Treat. 2019 Jun;175(3):595-603. doi: 10.1007/s10549-019-05191-2. Epub 2019 Mar 9.

  PMID: 30852761 RESULT

• Lynce F, Barac A, Tan MT, Asch FM, Smith KL, Dang C, Isaacs C, Swain SM. SAFE-HEaRt: Rationale and Design of a Pilot Study Investigating Cardiac Safety of HER2 Targeted Therapy in Patients with HER2-Positive Breast Cancer and Reduced Left Ventricular Function. Oncologist. 2017 May;22(5):518-525. doi: 10.1634/theoncologist.2016-0412. Epub 2017 Mar 17.

  PMID: 28314836 RESULT

MeSH Terms

Interventions

Trastuzumab; pertuzumab; Ado-Trastuzumab Emtansine

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Allison Moses
• Organization: MedStar

Allison.E.Moses@medstar.net

301-256-2728

Study Officials

• Sandra M Swain, MD

  Washington Cancer Institute at MedStar Washington Hospital Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2013
• First Posted: July 22, 2013
• Study Start: October 1, 2013
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2020
• Last Updated: May 10, 2022
• Results First Posted: February 2, 2021

Record last verified: 2022-05

Locations

US (2)